DESCRIPTION (adapted from the application's abstract): The Adult AIDS Clinical Trials Group (AACTG) is a multicenter, multidisciplinary clinical trials group dedicated to the study of HIV pathogenesis and therapy. Since its inception in 1987, the AACTG has evolved into a cooperative group consisting of the Central Group (composed of the Office of the Group Chair, Executive, Scientific and Resource Committee, a state-of-the-art laboratory network, a Community Constituency Group, and the Operations Center), 30 AIDS Clinical Trials Units (ACTUs) located at major academic medical centers, and the Statistical and Data Management Center. The AACTG has had an impact on elucidating the current understanding of AIDS pathogenesis and therapy, and has played a role in the development of novel trial designs and analysis strategies. AACTG clinical trials have helped define guidelines for the use of antiretroviral agents and for the prophylaxis and treatment of HIV- associated opportunistic complications. Over 200 manuscripts have been published by the AACTG describing this body of work since submission of the prior competing renewal application in 1995. Group productivity has been aided by collaborations with a wide variety of external investigators and laboratories, U.S. and international clinical trials networks, and members of the pharmaceutical and medical diagnostics industries. The AACTG proposes to build on its accomplishments with the goal of further reducing, and ultimately eliminating, HIV-associated morbidity and mortality. The applicants propose to undertake investigations in a structure that allows for a high degree of efficiency and flexibility in the design and implementation of a broad array of clinical trials with patient management principles, according to the applicant, which are reflective of contemporary clinical practice and designed to ensure the relevance of research findings. Over the next several years the Group proposes to address a number of issues including how best to: provide initial and subsequent treatment to maximally suppress HIV replication; provide optimum treatment strategies following treatment failure; develop approaches to individualization of therapy based on genotypic and phenotypic characteristics of the virus and/or host; eliminate reservoirs of HIV-1 in latently infected cells; ameliorate virologic, immunologic, pharmacologic, and behavioral factors (adherence) that contribute to treatment failure; incorporate new therapies and treatment strategies into future regimens; evaluate new strategies for enhancing immune reconstitution to HIV and OIs; and delay or prevent HIV disease progression, opportunistic complications, complications of therapy, and mortality. To accomplish this agenda, the Group requests funds for 35 ACTUs that are to be evaluated on objective performance criteria. New sites and laboratories have been added to the Group in order to provide additional expertise in virology, immunology, and pharmacology. The Group remains committed to enrolling women and minorities and to continuing support of the Minority AIDS Training Program.